Monday, 13 April 2015

Bar code of a killer!

Last night I watched the concluding part of the ITV drama "Code of a Killer", in which the Leicestershire police (led by DCS David Baker, played by David Threlfall) sought the help of (now Sir) Alec Jeffreys (played by John Simm) to identify the rapist and murderer of two young girls in the early 1980s. I discussed the background to the science in an earlier post, but here is a quick (and personal) summary of the Scientific "climate of technology and discovery" surrounding molecular genetics in the late '70s-early 1980s.
Whilst methods were developed as log ago as 1974 for gene sequencing (thanks to Fred Sanger, Walter Gilbert and Allan Maxam), by 1982, molecular biologists had access to the genomes of just two bacteriophages, along with the (rather modest, by today's standards!) human mitochondrial genome. And just in case you are too young to remember, finding a computer in a Biology lab in the early 1980s, to analyse the sequences, was truly exceptional. Most high profile molecular biology labs at this time had their sights firmly trained on the common features of gene sequences (which is of course of fundamental importance), however, when Alec Jeffreys arrived at the University of Leicester, he set out to explore the differences between the genes of closely related species. Around this time, Nobel Prizes were awarded for the discovery of the tools that Alec Jeffreys would employ in his work (Arber, Nathans and Smith: Restriction Enzymes) and work on the immune system had first produced monoclonal antibodies (Jerne, Kohler and Milstein) and then Tonegawa was recognised for his work on the genetic origins of antibody diversity. It was some time later that Sharp and Roberts were independently rewarded for their work in the late 1970s on the discovery of split genes (exons and introns), but such events were timely for Jeffreys to lay the foundations for DNA fingerprinting, or profiling. I should also mention that David Botstein had used restriction enzymes to expose subtle variations in genes, referred to as RFLPs (restriction fragment length polymorphisms), arising through the loss or gain of a restriction site through mutation. Finally, I should probably point out that whilst gene sequencing was now becoming popular in many research labs, it was largely a manual process and it would be some years before it would become automated to a level that large genome sequencing projects could be considered feasible. In fact, the method of choice for molecular analysis of DNA (and RNA) was Southern (or Northern) Blotting, the former technique being developed by Ed Southern, even though Kary Mullis had discovered the technique for PCR in 1980. At this point, I hope (presumably in vain) that I haven't left out any important discoveries! 

The challenge that Alec Jeffreys faced, is one of the most fundamental aspects of genome science: on the one hand Darwinian evolution leads us to look for the similarities between genes in say mice and men. However, what is important in forensics (and paternity testing) are the elements in our genomes that make us different. These are the "stutters" that are mentioned in the drama. The image on the left shows Alec holding an autoradiograph revealing a series of DNA fragments which have been "highlighted" through the use of a radioactive "probe" designed to "pick out"  DNA sequences complementary to the probe itself. In this way a scene of crime sample can be unequivocally identified as belonging to the suspect, or (importantly) NOT. Recall that the phenomenon of base pairing is a key component of the structure of DNA in which the bases G and C and A and T form "complementary" pairs. So, if a fragment of DNA contains the sequence 5'GATTCCGGATTCA3' (for example), then the probe sequence 5'TGAATCCCCGGAATC3' would "hybridise" to it. If the probe was radioactively (or fluorescently) labelled, then the complementary sequence separated on a gel (agarose for long fragments and polyacrylamide for short fragments of DNA) can be "visualised" using a suitable film or detector. When Alec Jeffreys is shown in episode one, trying various probes to explore similarities and differences in genes, his focus on the seal myoglobin gene is shown because this is where he obtained the first high quality data, from a highly variable sequence, linked to a common core sequence within an intron in the myoglobin gene. 

The second part of the drama begins with a press conference in which the police announce that their prime suspect has been excluded by genetic fingerprinting! There are few applications of science that have been so closely intertwined with the police and the legal profession. Ten years later, the US sports celebrity O.J. Simpson would be famously acquitted of the murder of his wife, following a high profile trial in which the evidence from genetic fingerprinting was dismissed, not because the science was suspect, but rather the "audit trail" of sample collection and analysis was shown to be unreliable. What I particularly liked about the second episode of Code of a Killer, is the recognition (and conviction) shown by DC Baker, that Scientific evidence will provide the truth. Moreover, we mustn't underestimate the importance of Alec Jeffreys' success in communicating this so effectively to the police officer. The other parallel I like in the drama, is that between the work of a principal scientist (PI) and that of a chief investigating officer (CIO): both involve the systematic collection, evaluation and rigorous testing of data. DC Baker's leadership of his team will be a familiar tale to many PIs, as he navigates  through misleading results (false leads) and the challenges of funding and competing priorities (budgets and politics!) to finally apprehend the killer (or more usually clone the gene!).

I am not sure that this production will receive the accolades reserved for great TV drama, but it does join a handful of productions in which the profound value of science to society is showcased effectively. I also managed to get over the somewhat hackneyed references to the "committed scientist burning the midnight, oil whilst neglecting his family", in episode one. In fact, the scene in the second part, in which Alec Jeffreys persuades the community to submit to testing, by holding aloft his own genetic fingerprint alongside that of the killer, is a lovely moment that in my view, fully vindicates the pursuit and public support for Blue Skies Science. If you have been fortunate enough to spend an evening chatting with Alec, or have been present at one of his seminars, you will undoubtedly share my view (and that of the people of Leicester, who awarded him the freemanship of the city in 1992!) that he is not only an outstanding scientist but an exceptional human being. I will leave you with the thought that occurred to me when Alec Jeffreys aligned the autorads of the sample taken from Colin Pitchfork and that recovered from a victim: Alec Jeffreys' greatest legacy may be to Human Justice and not Science!

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